Our basic goal is improved diagnosis and treatment of patients with hemostatic defects. In this grant we propose a study of the regulation of hemostasis. Normal coagulation involves activation of prothrombin and a study of its activation products both in vitro and in vivo is in progress. The main disease state we will study is von Willebrand's disease, which affects many areas of the hemostatic mechanism. We are studying the basic pathophysiology of von Willebrand's disease in pigs and have isolated the von Willebrand factor both in pigs and in humans. The investigation of normal and abnormal hemostasis is designed to give greater insight into the normal control of hemostasis and how symptoms arise and how laboratory tests become abnormal when the control is imperfect. BIBLIOGRAPHIC REFERENCES: Owen, C. A., Jr., Goldstein, N. P. and Bowie, E. J. W.: Platelet function and coagulation in patients with Wilson disease. Arch. Int. Med. 136:148-152, Feb., 1976. Fass, D. N., Brockway, W. J., Owen, C. A., Jr. and Bowie, E. J. W.: Factor VIII (Willebrand) antigen and ristocetin-Willebrand factor in pigs with von Willebrand's disease. Thromb. Res. 8:319-327, 1976.